Inborn errors of immunity (IEIs) can present atypically, including with autoimmune cytopenias or persistent viral infections. X-linked lymphoproliferative syndrome type 1 (XLP-1) is a rare primary immunodeficiency caused by mutations in the SH2D1A gene, characterized by hypogammaglobulinemia, Epstein–Barr virus (EBV) susceptibility, and risk of hemophagocytic lymphohistiocytosis (HLH).
A previously healthy 3-year-old boy initially presented with immune thrombocytopenic purpura at 1 year and 11 months, with good response to dexamethasone and intravenous immunoglobulin. Months later, he developed signs of lymphoproliferation, including generalized lymphadenopathy and hepatosplenomegaly. Persistent hypogammaglobulinemia and EBV infection were subsequently documented. Lymphocyte subset analysis was within normal ranges and bone marrow aspiration showed no pathological infiltration. Genetic analysis revealed a pathogenic mutation in SH2D1A, confirming the diagnosis of XLP-1. The patient was started on immunoglobulin replacement therapy and antivirals, with hematopoietic stem cell transplantation under consideration as definitive treatment.
This case highlights the need to suspect primary immunodeficiencies in pediatric patients with autoimmune cytopenias and recurrent viral infections. Early identification of XLP-1 enables targeted therapeutic interventions that significantly improve outcomes. The integration of clinical, immunological, and genetic findings was critical for diagnosis.
